tumor suppressor gene

‘Tis The Season To…..Mask Up Again??

"It's a bug hunt!"

-Private Hudson, in “Aliens”

"Influenza-like illnesses" are increasing at an alarming rate across the country. Yup, ‘tis the season for respiratory diseases and we have more than one to worry about. In years past we mostly worried only about the flu and, sometimes as an afterthought, colds, which aren’t of much concern. But in late 2019, a brand new and very weird bug appeared on the scene, SARS-CoV-2 that caused COVID. It seems that the bug and disease will be an annual guest from now on. This year, we also see a surge of a third bad bug, respiratory syncytial virus, or RSV. All these viruses cause what have been collectively labeled “flu-like illnesses” and together they seem to be worse this year than recent years. The CDC reports that hospitalizations for flu-like illnesses have been steadily rising and that the peak is still to come.

As a result, we are beginning to see increasing reports of a return to local mask mandates. In my own community of Madison, Wisconsin, two major health networks just announced their return, like a bad TV rerun. This includes the University of Wisconsin Health network, where I receive health care. Glad I kept a few masks on hand. What’s in your glove compartment?

I also have read where some grocery stores are now requiring masks. Some stores only require masks on certain days of the week so that customers can select to shop on mask-required vs mask-optional days. Some colleges and large companies reportedly also are beginning to require masks again. So far these mandates are very local and are not a national phenomenon. It is feasible that mask mandates in public spaces and especially for travel could increase if infections and hospitalizations get more serious.

As I often say in these blog posts, “we will see.”

Why is the flu and RSV, which have been around almost forever now causing more than their usual problems? A hint was presented in a blog post I published about a year-and-a-half ago, “What Happened To The Flu And Other Respiratory Diseases?”  In that apparently prescient post, I reported that the world had seen a huge reduction of all infectious respiratory diseases due to the protective non-pharmaceutical interventions (masking, sanitation, isolation, quarantines, closings, etc.) designed to physically protect people from the new coronavirus. They were so effective that some strains of other common infectious viruses are thought to have gone extinct!

That is great news! But, it also means that the world also missed its regular natural booster of common bugs and our herd immunity to them waned. Our youngest were never exposed to those bugs and the rest of us became less resistant to future exposure and that future is now. We are now paying the piper for that lapse in a “bug boost.” Hence, flu and RSV temporarily are having their way with us and enjoying it. At least they are not nearly as nasty as the coronavirus initially was and still could be with a couple of insouciant genetic tweaks.

“Influenza-like illness,” is a catch-all term coined by the CDC to corral COVID and the other two viral diseases. Together, the three have reached an epidemic point in the US and other places across much of the world. The Figure below shows that the US epidemic is currently hitting Southern States the hardest, but expect it to migrate Northward in the next few weeks.

What do the different colors in the Figure mean on a practical level? I can offer one anecdotal example. According to the map, New Jersey, while not a Southern State, still is being hit hard. A family doc wrote about a week ago that all the hospitals in his health system are at capacity. He was unable to send a patient to the preferred ER because its hospital was full due COVID, flu and RSV cases. And the patients with these flu-like respiratory infections who were filling the beds were not necessarily elderly. Most are in their 40’s-50’s. Unsurprisingly, the hospitals and clinics in his health system again require masks. Their staffing is becoming a critical issue as providers also become ill and turn into patients. This is becoming too reminiscent of the early stages of the COVID onslaught when hospitals where overwhelmed and medical personnel were dropping like flies. So far, this experience is sporadic across the US. But, it is becoming concerning.

ORI
Outpatient Respiratory Illness Activity Map Determined by Data Reported to ILINet
This system monitors visits for respiratory illness that includes fever plus a cough or sore throat, also referred to as ILI, not laboratory confirmed influenza and may capture patient visits due to other respiratory pathogens that cause similar symptoms. From the CDC.

The incidence of RSV is high. RSV hospitalizations have increased 60% nationwide over the past four weeks. A couple of deaths in children have been reported in my state. The vaccine for RSV is brand new this year and recommended for people over 65 and for kids; i.e., those at highest risk for severe disease. It definitely is worth it.

Flu is moderate right now, but expect it to soon blossom. Hospitalizations among all age groups increased by 200% for influenza in the past four weeks but still remain below Covid-19 and RSV hospitalizations. For now. They are expected to increase as the peak flu season has yet to arrive.

And then there is our relatively new friend, COVID. On a national level, COVID virus transmission is “very high.” After the post-Thanksgiving surge, as determined by monitoring viral loads in wastewater samples (“take-your-kids-to-work” days in that profession must be fun!), virus levels plateaued. But expect another sharp rise after the Christmas/New Year’s holidays. We have consistently seen this pattern in previous years.

Cov-2 is one of the most mutable viruses that the world has inflicted on us. That means we are constantly seen new variants arising. Surprise, the Omicron subvariant JN.1 is coming onto the scene. It’s the spawn of variant BA.2.86, which was discovered over the summer and was concerning because it came out of nowhere with a whopping 35 mutations in the spike protein (the more mutations, the greater the chance for another very nasty bug). While BA.2.86 caused a comparatively mild disease, it quickly mutated to JN.1 with just an additional single change in the spike protein that made it much more infectious, but it still remains fairly mild. With just one mutation, it became the fastest-spreading CoV-2 variant in the past two years. With all its changes, JN.1 is so different from its Omicron grandparent that there is considerable scientific debate about whether JN.1 should be given its own Greek letter designation, Pi. A weighty debate indeed.

But, a bigger question is whether COVID hospitalizations will follow wastewater sampling trends that show JN.1 (or Pi) viral levels surging through the world, especially in the US where vaccination rates are low. It is concerning that the UK and Singapore, which have high vaccination rates, are now seeing a steep increase in hospitalizations due to JN.1 (or Pi). So why not expect the same or even worse in the undervaxed US? Last week, the CDC warned about such a potentially huge impact due to the wretched combination of low US vax rates and the highly infectious JN.1 (or Pi) virus. As Private Hudson (aka Bill Paxton) in the movie Aliens might say, thanks to the antivaxers, “Game over, man! Game over!”

Also of new concern is that some scientists are now beginning to believe that COVID infection could be damaging our immune systems. If true, that could make infected people even more vulnerable to the other bugs out there such as flu, RSV, and others including bacteria and fungi. COVID could also cause immune dysregulation leading to new-onset autoimmune diseases. So get your COVID vaccines! They can protect you against illness beyond COVID!!

Finally, another concern is that the rapid home tests for COVID are proving to be only 30% reliable very early after infection before symptoms start. In other words, if you believe you have been exposed to COVID, but your home test comes up negative, don’t necessarily believe it. Retest yourself 24, or preferably 48 hours later or when you show symptoms like a fever, cough, etc. If that second test also is negative, you have pretty good confidence you are COVID free and have some other bug.

The pragmatic bottom line. There is a lot of coughing, sneezing and other respiratory distress going around, and it will increase in coming cold weeks as we bundle up and crowd around others indoors. To improve your odds of staying healthy, remember these things:

  • Limit your time around indoor crowds.
  • If you have indoor gatherings, crack your windows and bring out the fans to increase air circulation and air exchange with the outdoors. There is very good evidence that good ventilation really matters and that the amount of viruses we breathe in makes a big difference in terms of whether we get sick and how sick we get. It is worth a few extra dollars on the heating or electricity bill to avoid nasty illness.
  • Room air filters are also a good idea.
  • Get vaccinated!
  • Wash your hands often.
  • If you do get sick, STAY HOME! I have always hated the “brave” soul who came to work with a cough and sneeze. Don’t share your agony!!
  • And there are the good old fashioned masks for use in crowded places, especially in auditoriums, on planes, and other packed indoor situations. I don’t care what the naysayers say about masks, they are flat wrong. They don’t think twice when a store sign requires shoes and shirts to enter. So why do masks bother them so much? They WORK as I have written here before, over and over. Empirical evidence proves masks work. That is why the entire medical profession continues to use them.

Finally, as I have repeatedly admonished, please get vaccinated. Vaccine and booster uptake for all three viruses has been dismal this year. Failure to vax is a major driver in the surge of the flu-like respiratory diseases we are seeing. If you have not gotten vaccinated for all three circulating viruses, why the heck not?? It is way better to prevent disease than to treat disease. A sore arm is much less of an inconvenience than suffering the flu, RSV or lying in a specialized hospital bed turned on your stomach breathing with a ventilator because of COVID.

As I have written in these pages, having COVID can be worse than any flu you ever had. It also puts adults at risk for dealing with weeks of long COVID and getting new-onset diabetes and immune dysfunction. COVID also is much worse than the flu for many kids and puts them at risk for multi-system inflammatory syndrome (MIS).

Why risk what can be prevented by a simple vaccination?

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Are COVID And Cancer Connected?

Nothing surprises me, I’m a scientist.” 

                            -Indiana Jones   

In 2019, the world was introduced to a brand new pathogen, the SARS-CoV2 coronavirus, that caused a brand new, and very odd disease, COVID-19. Between then and now, your humble bloggeur has penned 153 blog posts, many of which focused on how strange the disease is and describing our learning process as we figured it out on the fly. Many of these posts were necessarily equivocal because we simply did not have enough information to make firm conclusions on how the virus affects different people. Over time, we learned how to better treat the disease, and that learning curve continues. It was necessary to end many blog posts with the weak statement, “We will see.” Well we are still seeing and learning about this odd malady that consists of a melody of symptoms across myriad organs.

Research is now beginning to reveal a possible link between CoV-2 infection and cancer. As before, these observations are preliminary and will be further scrutinized, but they are bolstered by the discovery of a possible mechanism that could explain how the CoV-2 virus might cause cancer.

We know of many different viruses that cause cancer in animals. We also have a good understanding of how the viruses do that. There also are a few viruses, but not many, that cause human cancer, and we also mostly understand how they exert their oncogenic effects. These human cancer viruses include human papilloma virus (HPV), which causes cervical, and head and neck cancers. Hepatitis B virus can lead to liver cancer. Human T cell leukemia virus causes leukemia, and Epstein Barr virus can lead to lymphoma and a few other types of cancers. And so on.

To date, there has been very little association between any coronaviruses and cancer in animals or humans. But, that might be changing.

Several recent papers have revealed a genetic link between COVID-19 and cancer. One paper showed that people with an increased genetic risk of COVID-19, were also at increased genetic risk of developing endometrial cancer. The limitation of this study is that it cannot distinguish between a correlated high risk of COVID and cancer, vs whether COVID causes the cancer. It is the old conundrum of discerning between correlation vs cause-and-effect.

A second study incrementally advanced the above findings. Using a low resolution genetic mapping technique called genome-wide association, it found a positive correlation (there is that “C” word again) between people genetically predisposed to both severe COVID and increased risk for endometrial cancer. While still a correlation, one would predict that if there was a cause-and-effect relationship between COVID and cancer, that the risks for both would be similar. This is what the study showed.

Finally, a third study uncovered a possible mechanism by which SARS-CoV-2 could cause cancer. Having a possible mechanism in hand bolsters the possibility that the theoretical link between COVID and cancer is true. But first, a little back story about cancer genetics.

Cancer genetics.  Basically, cancer is a genetic disease. That does not necessarily mean that it is always inherited. Most cancers probably are not. But, when the genetic fidelity of a cell messes up, it can become immortal, can grow in an unregulated fashion, and can become resistant to normal signals that should cause it to die. In a nutshell, that is cancer. Generally speaking, there are two kinds of genes that contribute to this process. 1) Dominant acting oncogenes are aberrant genes that when expressed, drive the above activities. 2) Suppressor genes provide brakes to the above activities, and when absent, the brake is released. In both cases, genetic abnormalities either activate oncogenes to drive cell immortality and growth, or eliminate expression or activity of tumor suppressor genes removing the brakes to cell growth. Usually, cancer is a stepwise process in which cells sequentially accumulate different abnormal oncogenes and suppressor genes. The combination of which leads to full blown cancer.

One of the first tumor suppressor genes to be identified is called P53. In several different tumors, it was noticed that expression of this gene was missing due to DNA mutation. Further research showed that when expressed, P53 provides a brake on cell growth. There are many ways that P53 can be inactivated. Genetic mutation can prevent its expression, or hinder its function. We also know that a few viruses that cause cancer in people, like hepatitis B virus and Epstein-Barr virus, produce proteins that can interact with and inactivate the P53 gene product. A paper published in November, now reports that two CoV-2 proteins interact with cellular proteins to stimulate complex pathways that lead to degradation of the P53 gene product, releasing the anti-cancer brake in infected cells. The research also shows that that P53 activity is lost in patients with severe COVID disease but not in those with less severe illness. P53 loss also correlates with length of COVID symptoms. In other words, the more severe the COVID disease, the greater the chance that the P53 brake is lost.

This observation does not yet prove that inhibition of P53 by the CoV-2 virus causes cancer, but it now presents an important hypothesis that will be given much research attention. Questions remain regarding the association between CoV-2 infection and cancer. Also, since COVID infections are generally relatively short-lived, how long does the loss of P53 function last? Are long-COVID patients at increased risk for chronic loss of P53 and cancer? Is this loss of function sufficient to launch the multistep pathway that leads to cancer?

Once again, we will see.